DESCRIPTION (Applicant's Description) Although tobacco and alcohol exposure are the major determinants of risk for the development of squamous cell carcinoma of the head and neck (SCCHN), host-specific factors also influence the predisposition to cancer development. Genetic alterations that occur in the histologically normal mucosa prior to phenotypic transformation are likely to represent early events in carcinogenesis. We have previously shown that TGF-alpha and its receptor, EGFR, are up-regulated at both the mRNA and protein levels in both tumors and histologically normal mucosa biopsy samples from patients with SCCHN when compared with levels in control normal mucosa from individuals without cancer. Subsequent analysis of 21 SCCHN patients revealed the striking finding that all patients with higher levels (greater than 4x control) of TGF-alpha and EGFR mRNA and protein expression, as evaluated by computerized image analysis of immunohistochemical staining, died of progressive carcinoma at a mean of 28 months (range 7-54 months) while all patients who had low TGF-alpha and EGFR levels (0-2x control) in their primary tumors were alive without evidence of disease (p is equal to 0.001). We propose to expand this observation in primary tumor tissue to an additional group of SCCHN patients who have also provided serum samples to our head and neck cancer serum bank at the time of diagnosis and on whom adequate follow-up data is available. In addition to quantitating protein levels in the primary tumor, we will determine whether elevated TGF-alpha and EGFR levels in the tissues are correlated with serum levels. Since we have serial serum samples collected over time, we can also examine the relationship between tumor excision, cure, disease recurrence, second primary tumor development and serum TGF-alpha and EGFR levels. The results of this study will verify whether TGF-alpha and EGFR expression levels in the primary tumor correlate with survival and determine if serum can be used as a surrogate for tissue. Since TGF-alpha and EGFR are up-regulated in the histologically normal mucosa from SCCHN patients, the detection of elevated TGF-alpha and EGFR in biopsy specimens (or peripheral blood) may provide an important new method of screening for high risk individuals.